Artery- and vein-specific proteins and uses therefor

Abstract

Arterial and venous endothelial cells are molecularly distinct from the earliest stages of angiogenesis. This distinction is revealed by expression on arterial cells of a transmembrane ligand, called EphrinB2 whose receptor EphB4 is expressed on venous cells. Targeted disruption of the EphrinB2 gene prevents the remodeling of veins from a capillary plexus into properly branched structures. Moreover, it also disrupts the remodeling of arteries, suggesting that reciprocal interactions between pre-specified arterial and venous endothelial cells are necessary for angiogenesis. This distinction can be used to advantage in methods to alter angiogenesis, methods to assess the effect of drugs on artery cells and vein cells, and methods to identify and isolate artery cells and vein cells, for example.

1. A method of inhibiting angiogenesis in a mammal suffering from a disease or disorder characterized by undesirable or excessive vascularization or vascular permeability, comprising administering to the mammal an amount of an antagonist of Ephrin B2 or an antagonist of EphB4 which is effective for inhibiting angiogenesis in the mammal, wherein the antagonist is an Fc fusion molecule with the extracellular domain of EphB4 or an Fc fusion molecule with the extracellular domain of Ephrin B2, and wherein the antagonist is in a non-cluster form. 
     
     
       2. The method of  claim 1 , wherein the mammal is a human. 
     
     
       3. A method of inhibiting angiogenesis in a mammal, comprising administering a therapeutically effective quantity of an antagonist of Ephrin B2 or an antagonist of EphB4, wherein the antagonist is a soluble antagonist comprising an extracellular domain of Ephrin B2 or a soluble antagonist comprising an extracellular domain of EphB4, and wherein the antagonist is in a non-cluster form. 
     
     
       4. The method of  claim 3 , wherein the mammal is a human.